口服胶原肽对人体皮肤生物物理特性的影响：叙述性综述

Abstract 原文摘要

Abstract

The skin not only provides protection and sensory functions for the body, but healthy skin also enhances self-esteem. Moreover, altered cutaneous function contributes to the development of extracutaneous disorders. Therefore, great efforts have been made to identify agents and natural ingredients that are safe and effective to improve cutaneous function. In this narrative review, we searched PubMed and Google Scholar for literature on the effects of collagen peptides on skin biophysical properties. Studies have demonstrated that oral peptide improves several cutaneous functions, including stratum corneum hydration, epidermal permeability barrier, elasticity, firmness and roughness, in part via upregulation of keratinocyte differentiation, epidermal lipid synthesis, hyaluronic acid and collagen synthesis, and inhibition of inflammation, in addition to stimulation of fibroblast proliferation and aquaporin 3 expression. However, the heterogeneity among the included studies and their limited sample sizes preclude firm conclusions regarding the benefits of oral collagen peptides for cutaneous biophysical properties. Further research is needed to assess the efficacy of different collagen peptide sources and types across individual skin biophysical outcomes.

Keywords: collagen peptide、skin barrier、stratum corneum hydration、skin aging、wrinkle、elasticity

Introduction

Cutaneous function not only dominates the cosmetic appearance but also influences cutaneous and extracutaneous conditions. Previous studies demonstrated that disruption of epidermal permeability barrier function stimulates epidermal proliferation, cytokine production, inflammatory cell infiltration and T cell proliferation, in addition to increase epidermal lipid synthesis and lamellar body secretion. 1–3 Moreover, acute disruption of epidermal permeability barrier function increases expression levels of mRNA for proinflammatory cytokines in the skin and serum levels of proinflammatory cytokines in mice. 4 Furthermore, low humidity decreases stratum corneum hydration levels, 5 resulting in increased inflammatory infiltration and expression levels of proinflammatory cytokines in the skin. 6–8 Importantly, stratum corneum hydration levels correlate negatively with serum cytokine levels in humans. 9 This line of evidence suggests the contribution of epidermal dysfunction, including reduced stratum corneum hydration levels, to systemic inflammation, leading to the development of some systemic disorders. 10 Additionally, healthy, beautiful skin increases self-esteem and social interaction. Some skin conditions such as wrinkles can affect the appearance of the skin and adversely impact mental health. Maintenance of a healthy and beautiful skin benefits overall well-being. 11 Because of the pivotal role of skin condition on overall health, scientists are devoted to identifying agents, including natural ingredients, that can improve cutaneous function.

Many natural ingredients, including glycerol, hyaluronic acid, ceramides and peptide, are effective in improving cutaneous functions. For instance, both glycerol and hyaluronic acid are effective for moisturizing the skin. 12 , 13 Although negative results have been reported, 14 studies have shown improvement of stratum corneum by either topical or oral administration of ceramides. 15–17 Recently, the beneficial effects of edible ingredients on cutaneous function have attracted attention because of their superior efficacy and safety. 18 , 19 Among the edible ingredients, peptide, derived from protein, is demonstrating multiple benefits for cutaneous function.

A peptide is a molecule containing two or more amino acids. According to the length of the chain, peptides can be classified into short-chain and long-chain peptides. The former, also termed “oligopeptides”, usually have fewer than 20 amino acids, including dipeptides (2 amino acids), tripeptides, 3 and tetrapeptides, 4 while long-chain peptides are polypeptides, containing more than 20 amino acids. Orally ingested collagen is digested and hydrolyzed to peptides and amino acids in the gut, and is subsequently absorbed into the circulation. 20 In rats, the serum levels of di- and tri-peptides reached as high as 105 nM/mL two hours after intragastric administration of collagen hydrolysate. 21 In humans, the absorption rate for tripeptide of glycine, L-proline and 3-hydroxy-L-proline (Gly-Pro-Hyp) is lower than that for prolylhydroxyproline (Pro-Hyp) (0.663 ± 0.022 nmol/mL·h vs 163 ± 1 nmol/mL·h) following oral ingestion of 25 g of fish gelatin hydrolysate. 22 14C-labelled Pro-Hyp and Pro can be observed in the rat skin 30 min after oral administration of [ 14 C]Pro-Hyp. 23 Hence, either collagens or peptides have been used to study their influence on cutaneous function.

In comparison to topical application, oral intake of collagen peptides can be distributed to whole body and more convenient to use. Therefore, this narrative review focuses on the benefits of oral collagen peptides and their combination with other ingredients in the skin. Relevant literature was searched on PubMed and Google Scholar from inception to October 2025. The search terms included “hydration”, “transepidermal water loss”, “elasticity”, “firmness”, “wrinkle”, “peptide”, and “collagen”. The inclusion criteria comprised peer-reviewed publications involving oral collagen or peptides in humans, with full texts available in English. The exclusion criteria included studies not published in English or not peer-reviewed, collagen/peptides that were not orally administered, and studies not conducted in humans. All articles were first assessed based on their titles and abstracts, and then the full texts were reviewed. Thus, this narrative review summarizes the evidence from the relevant literature regarding the regulatory role of oral collagen peptides in cutaneous biophysical properties 24–71 ( Table 1 ) and the underlying mechanisms.

Table 1 Influence of Oral Collagen Peptide on Skin Biophysical Properties

Stratum Corneum Hydration

Stratum corneum hydration levels not only indicate cutaneous and extracutaneous functions but also regulate these functions. 72 Previous studies demonstrated that stratum corneum hydration levels are associated with serum HbA1c and some proinflammatory cytokine levels in humans. 9 , 72 , 73 Improvement in stratum corneum hydration levels can improve some health-related conditions. 10 Although numerous topical agents can improve stratum corneum hydration on the treated areas, orally administered products, including collagen peptides, exhibit advantages over topical ones, including easy administration and the ability to improve hydration on the entire body. Previous study showed that daily oral intake of 2.5g of bovine collagen peptide for 4 and 8 weeks increased stratum corneum hydration levels by 21% and 29%, respectively, on the forearm, whereas the placebo did not significantly alter the stratum corneum hydration. 27 Studies have also demonstrated the positive effects of oral collagen peptide from those derived from fish gelatin on stratum corneum hydration. For example, Inoue et al reported that oral collagen dipeptides, prolyl-hydroxyproline and hydroxyprolyl-glycine, significantly improved stratum corneum hydration on both the canthus and cheek after 4-week intake, with further increase after 8-week intake. 40 Oral administrations of collagen peptides derived from other sources such as chicken sternal cartilage and fish gelatin also improve stratum corneum hydration. 41 , 52 However, controversial results have also been observed. Tak et al reported that oral administration of fish collagen tripeptides containing 3.2% of glycine, proline and hydroxyproline at a daily dose of 1000 mg for 12 weeks did not significantly increase stratum corneum hydration levels in comparison to placebo (16.50 ± 21.7 vs 12.44 ± 21.7, p > 0.05). 45 In contrast, another study showed that intake of 1000 mg fish collagen tripeptides containing 3.0% of glycine, proline and hydroxyproline daily for 12 weeks dramatically increased stratum corneum hydration levels (61.14 ± 13.31 vs 53.02 ± 13.59, p < 0.01). 44 The participants in both studies were women between 40 and 60 years of age, and the tripeptides and treatment plans were similar. However, the former study used peptide from Oreochromis niloticus , while the latter was from Pangasius hypophthalmus . A recent study showed that oral administration of low molecular weight bovine collagen peptides for 12 weeks did not remarkably increase stratum corneum hydration in women aged 45 to 60 years old (p > 0.05 vs placebo). 24 Whether the various sources of collagen account for the differences in efficacy are unknown. Thus, the underlying mechanisms contributing to the discrepant results are unclear. Further studies are needed to validate the effect of peptide on stratum corneum hydration.

Epidermal Permeability Barrier

Epidermal permeability barrier does not only prevent movement of substances in and out of skin but also regulates several cutaneous and extracutaneous functions, including keratinocyte proliferation, epidermal lipid production and inflammation. 1 , 74 Improvement in epidermal permeability barrier function is a valuable approach in the management of some skin conditions such as inflammatory dermatoses. 75–78 Among the agents that improve epidermal permeability barrier, a number of studies demonstrate that oral intake of collagen peptides is safe and effective.

Previous study showed that oral administration of a tripeptide (glycine, proline and hydroxyproline) at a daily dose of 1 gram for 12 weeks induced a greater reduction in TEWL on the antecubital fossa than placebo (15% vs 6%) in middle-aged women (40–60 years old). 45 The benefit of collagen on TEWL has also been demonstrated in individuals aged 31–48 years, who exhibited lower TEWL compared to a placebo following an 8-week oral intake of 10 grams of fish collagen peptide with 400 mg of ornithine (11.5 ± 4.2 vs 16.2 ± 3.4, p < 0.05). 50 Moreover, oral peptide also improves epidermal permeability barrier function in individuals with sign of aging. Kim et al reported that oral intake of 500 mg of collagen peptide twice daily for 12 weeks significantly lowered TEWL than placebo (22% vs 13%, p < 0.01) in individuals with periorbital wrinkles (score of the 10-grade crow’s feet photo scale ≥3) and dry skin (hydration levels < 50 a.u.). 55 Another study showed that women aged 35–45 years orally took placebo for 30 days did not change TEWL on the cheek at all. Afterward, the participants were orally given 5 grams of fish collagen peptide and antioxidants daily for 30 days, resulting in a marked reduction in TEWL, with a significant reduction at 60 days. 56 However, several studies have also shown no significant changes in TEWL following the administration of various sources of collagen peptide, including porcine, eggshell membrane, chicken sternal and fish. 33 , 36 , 37 , 59 It is worth noting that all these studies were performed in a relatively small group of subjects (fewer than 100 individuals). Studies with larger cohort are warranted to evaluate the efficacy of oral peptide for epidermal permeability barrier function.

Skin Elasticity

Skin elasticity refers to the skin’s ability to stretch and return to its original shape and directly influences both the appearance and function of our skin. Both extrinsic and intrinsic aging decrease skin elasticity, in part attributed to reduced production and/or increased damage of collagen and elastin networks. Maintaining optimal skin elasticity is not only vital for aesthetic purposes but also for overall skin health. Although strategies such as diet rich in antioxidants, sun protection, and the use of targeted skincare products can help support the skin’s structural integrity, evidence also indicates the benefits of collagen peptides for skin elasticity.

Oral intake of 10 grams of bovine collagen peptide enriched in alanine, arginine, aspartic acid, glutamic acid, glycine, and other amino acids daily for 8 weeks significantly increased skin elasticity from 39.9 ± 4.7 mPa at baseline to 43.0 ± 7.4 mPa at week 8 (p = 0.009 vs baseline; p = 0.017 vs placebo). 25 The skin elasticity remained higher even 4 weeks after the treatment (41.8 ± 4.3, p = 0.027 vs baseline). In contrast, the placebo treatment did not significantly change the skin elasticity (39.1 ± 6.0 mPa at baseline vs 40.3 ± 3.3 mPa at week 8, p > 0.05). Moreover, daily intake of either 2.5 or 5.0 grams of porcine collagen peptide for 4 weeks increased skin elasticity levels by 7% (p < 0.05 vs placebo), with more prominent effect in subjects aged over 50 years. 33 Similarly, oral administration of 1650 mg of a fish-derived dipeptide (hydroxypropyl-glycine and prolyl-hydroxyproline) daily for 12 weeks markedly increased skin elasticity compared to the placebo (p = 0.013 vs placebo) in women with skin aging sign such as dry facial skin (stratum corneum hydration levels ≤ 49 a.u.) and crow’s feet. 46 Improvement in skin elasticity has also been observed following oral administration of collagen peptide derived from other sources such as eggshell membrane and chicken sternal cartilage. 37 , 38 Taken together, this line of evidence suggests the potential utility of collagen peptide in improving skin elasticity.

Skin Firmness

Skin firmness is a key aspect of skin health and appearance. As we age, the skin undergoes natural changes due to a decrease in collagen and elastin production, leading to a loss of skin firmness. In addition to environmental factors such as sun exposure and pollution, certain diets, including collagen peptide, also affect the skin firmness. For example, middle-age women ingested 2.5 grams of bovine collagen peptide, with an average molecular weight of 4 kDa and 40% of it being <1 kDa, once daily increased skin firmness by 4% on day 28, and 12% on day 84 (p <0.001 vs placebo at both time points). 24 Another study involving a small group of women aged 45 to 60 years demonstrated a greater increase in skin firmness (22% higher the placebo) following 12-week ingestion of 10 grams of collagen peptides derived from fish. 48 Interestingly, skin firmness in women aged 45–65 years was increased by 56% and 99% (p < 0.0001 vs baseline), respectively, following one-month and 3-month ingestion of a combination of bovine collagen peptide with other active ingredients (hyaluronic acid, vitamins A, C, D, and E). 30 Likewise, women with signs of skin aging orally ingested a mixture of collagen peptides, vitamin C, and natural antioxidants (extracts of H. sabdariffa and A . chilensis ) for 8 weeks, resulting in a 28% increase in skin firmness from baseline and a 38% increase by 12 weeks (p < 0.001). 69 Together, this evidence suggests a possible synergistic benefit of collagen peptides in combination with other active ingredients for skin firmness.

Wrinkles

Wrinkles are among the most noticeable signs of aging, resulting from a complex interplay of factors, including a decline in collagen and elastin production, sun exposure, dehydration, and lifestyle choices (such as smoking and diet). While wrinkles are typically associated with intrinsic chronological aging, they can also develop as a result of extrinsic aging. As the skin loses its elasticity and moisture over time, the formation of wrinkles becomes more pronounced, prompting individuals to seek various treatments, including topical creams, medical procedures such as laser and light therapies, and systemic regimens. The latter approach is likely to improve wrinkles over a larger area compared to the former two because of potential distribution of active compounds throughout the skin after systemic administration.

An interesting study by Inoue et al showed that oral fish dipeptide (prolyl-hydroxyproline and hydroxyprolyl-glycine) at a daily dose of 5 grams for 4 weeks significantly decreased both wrinkle area (p < 0.05 vs baseline) and wrinkle depth (3% reduction) (p < 0.05 vs both baseline and placebo). Eight-week ingestion of fish dipeptide markedly decreased the number (19%) and depth of wrinkles (7%) (p < 0.05 vs baseline and placebo for all). 40 Moreover, the wrinkle volume was decreased by 9% and 25%, respectively, following daily ingestion of 2.5g of bovine collagen peptide for 4 and 8 weeks. However, the oral intake of placebo did decrease wrinkle volume (1.58 ± 0.17 vs 1.49 ± 0.35 at baseline). 27 Similarly, oral intake of 2.5 grams of porcine collagen peptide for 4 weeks decreased the eye wrinkle volume by over 9.0% in comparison to the placebo group (p < 0.05), with a further decrease by 8 weeks (25% reduction). This positive effect on wrinkle volume persisted 4 weeks even after the last intake of peptide (11.5% reduction from baseline, p < 0.01 vs placebo). 27 Likewise, oral intake of 2.5 grams of bovine-derived collagen peptide along with acerola extract, vitamins C and E, and others daily for 12 weeks decreased the wrinkle depth by 27% (161.6 ± 11.4 µm vs 118 ± 16.4 µm) while the placebo did not dramatically change the wrinkle depth (6%) (161.7 ± 13.0 µm vs 151.4 ± 15.9 µm) (p < 0.001 vs placebo). 31 Additionally, oral administration of a capsule containing 300 mg of hydrolyzed collagen type-II derived from chicken sternal cartilage, and others (glycosaminoglycan, chondroitin sulfate and hyaluronic acid) twice daily for 12 weeks significantly reduced the number of facial wrinkle (p < 0.001 vs baseline) while placebo (cellulose) alone had no effect. 38 But whether the combination of collagen peptide and other active ingredients, such as acerola extract, and vitamins C and E, has additive or synergistic benefits on skin wrinkle remains to be evaluated.

Furthermore, the positive effects of oral collagen peptide on skin wrinkle have also observed in women with signs of skin aging, such as dry facial skin, lack of facial elasticity and density, wrinkles on crow’s feet area graded ≥2 according to the Skin Aging Atlas Vol. 2. Vleminckx et al reported that oral intake of 5 grams of peptide derived from porcine skin, but not placebo, daily for 4 weeks decreased wrinkle depth by 5% (p = 0.001 vs baseline. 34 In contrast, a study showed that intake of collagen drink for 8 weeks did not significantly improve facial wrinkles in women. 57 Nevertheless, this body of evidence indicates that various sources of collagen peptides can reduce both the depth and the number of wrinkles.

Safety

Generally, oral collagen peptides are safe. For example, oral ingestion of fish collagen peptide for 8 weeks did not induce any significant changes in a panel of biomarkers in circulation, including albumin, glutamic pyruvate transaminase, alkaline phosphatase, γ-glutamyltransferase, glutamic oxaloacetic transaminase; lactate dehydrogenase, blood urea nitrogen, urinary acid, and creatinine phosphokinase. 40 But few mild adverse reactions have been observed. One study observed that three females suffered from mild heaviness, mild pain and stomach bloating, although a 57-year-old woman had severe symptoms, leading to withdraw from the study during a 12-week period of study. 68 Another study reported that 1 out of 20 subjects stopped collagen peptide because of gastrointestinal problems. 29 In a study involving 116 subjects, only one person experienced mild red rash on the face, which resolved without any treatment after discontinuation of taking collagen peptide. 30 Because of the lack of placebo control, it is not clear whether these adverse events were caused by peptides or additives in the formulations. Some of adverse reactions may not be related to collagen peptides. For example, 18 adverse events were reported in a group of participants taking collagen peptide. Only one adverse event was likely related to collagen peptide. 48 However, a solid conclusion on the safety cannot be drawn because of the relatively small sample sizes in these studies.

Underlying Mechanisms

Although a number of studies have demonstrated the benefits of oral collagen peptides for skin functions, the underlying mechanisms remain unclear. Based on the changes in the skin functions, these peptides likely regulate the functions of either keratinocytes, fibroblasts, or both. Both stratum corneum hydration and epidermal permeability barrier function are largely determined by the keratinocyte function, while fibroblast function primarily governs skin elasticity, wrinkles, and skin firmness.

Keratinocyte Functions

Both stratum corneum hydration level and transepidermal water loss rate, an indicator of epidermal permeability barrier function, reflect epidermal functions. Hyaluronic acid and filaggrin play a crucial role in stratum corneum hydration and epidermal permeability barrier function. 79–83 Previous studies showed that Aspergillus oryzae -fermented wheat peptone increased stratum corneum hydration and lowered transepidermal water loss in humans, paralleled by remarkable increases in expression levels of genes for filaggrin, transglutaminase-1, and hyaluronic acid synthase 1–3, possibly mediated by activation of p44/42 MAPK signaling pathway in keratinocyte cultures because inhibition of this pathway attenuated the positive effects of Aspergillus oryzae -fermented wheat peptone on the skin. 84 , 85 In murine model of skin aging, collagen peptide increases hyaluronic acid, filaggrin and involucrin content in the skin 86 , 87 and expression of hyaluronic acid synthase 1,2, 87 , 88 while decreasing hyaluronidase 1 and 2 expression. 87 In keratinocyte cultures, collagen peptide at a concentration of 200 g/mL induces 2- to 4-fold increases in the expression levels of mRNA for hyaluronic acid synthase, filaggrin and aquaporin 3. 89 The latter is a positive determinant of both stratum corneum hydration and epidermal permeability barrier function. 90 , 91 Moreover, collagen peptide increases sphingolipid production in keratinocyte cultures. 92 In addition, some proinflammatory cytokines inhibit expression levels of differentiation marker-related proteins, tight junction proteins and lipid production, leading to a defective permeability barrier. 93 , 94 Some peptides inhibit expression levels of proinflammatory cytokines, such as IL-6, IL-1, TNF, and inducible nitric oxide synthase, while increasing tight junction protein expression (claudin 1, occludin and zonula occludens 1) in vitro and in vivo. 95 , 96 Interestingly, ceramide and peptide synergistically increase these gene expression. Apparently, some peptides, such as bovine bone derived peptides, do not affect stratum corneum hydration and hyaluronic content but increase collagen content, at least in mice, suggesting differential effects of certain collagen peptides on keratinocytes and fibroblasts. 97 Together, the benefits of collagens and peptides on stratum corneum hydration and epidermal permeability barrier can be attributable to increases in expression levels of epidermal differentiation marker-related proteins, tight junction proteins, aquaporin 3, hyaluronic acid, and decreases in proinflammatory cytokines.

Fibroblast Functions

The influence of collagens or peptides on fibroblast functions can be summarized as increases in cell viability, proliferation and migration, 64 , 85 , 88 , 98 stimulation of collagen and elastin synthesis, 24 , 85 , 88 inhibition of cytokine and matrix metalloproteinase 1, 3 expression in cell cultures. 24 , 64 , 85 , 88 , 99 , 100 The stimulation of collagen synthesis is in part mediated by TGFβ/Smad signaling pathway 101 , 102 and inhibits the matrix metalloproteinase expression by inhibiting the MAPK/AP-1 signaling pathway and upregulating TGF-β/Smad signaling pathway. 102 Additionally, peptide-induced antioxidation can also contribute to the improvement of fibroblast functions. For example, porcine placenta peptide dose-dependently increases in expression levels of glutathione peroxidase 1 mRNA in mouse skin. 100 Similarly, fish collagen/peptide decreases reactive oxygen species in vivo and in vitro , 101 , 102 and increases intracellular superoxide dismutase and glutathione peroxidase content in mice. 101 It appears that the efficacy of collagen/peptide on fibroblast function varies with the sources of the peptides. One study demonstrated the collagen peptide from cod fish scale exhibited superior benefit on fibroblast viability, antioxidant, and collagen synthesis to the other sources of collagen peptides (tilapia fish scales, cowhide, pig skin and chicken bone). In contrast, cowhide-derived collagen/peptide is more potent than other sources of collagen/peptide in upregulation of hyaluronic acid synthesis. 64 Taken together, the collagen or peptide-induced improvements in wrinkles, skin firmness, and skin elasticity can be attributed to the stimulation of fibroblast proliferation, collagen production, antioxidants, inhibition of inflammation, and matrix metalloproteinases.

Evidently, both collagen peptides and their metabolites regulate fibroblast function. Several studies demonstrate that collagen peptides stimulate fibroblast proliferation and collagen synthesis in vitro , 85 , 88 , 98 , 101 , 103 indicating the direct action of peptides on fibroblasts. Studies also show the regulatory role of collagen peptide metabolites in fibroblast function. 99 Moreover, human fibroblasts grow slower in serum-free medium than in medium containing 10% fetal calf serum (p < 0.0001). Human serum hydroxyproline levels, not chondroitin sulfate, increase by 88% 140 min following ingestion of fish cartilage peptides. Human serum from subjects taking fish cartilage peptides is more potent than that from individuals without taking peptides in stimulation of fibroblast growth and hyaluronic acid production (p < 0.0001). In addition, human serum only from subjects taking fish cartilage peptides, but not from individuals without taking peptides or fetal calf serum, increases elastin synthesis in fibroblast cultures (p < 0.01 vs fetal calf serum; p < 0.0001 vs serum from individuals without taking peptides). A similar pattern of effects of these serums on matrix metalloproteinases and TGF-β is also observed. 99 In comparison among different peptides, dipeptide (proline-hydroxyproline) at a concentration of 200 M increases cell viability by 17% (p < 0.05 vs control). Cell viability is not significantly affected by either other dipeptides (alanine-hydroxyproline, isoleucine-hydroxyproline, hydroxyproline-glycine), tripeptides (glycine-proline-hydroxyproline, proline-hydroxyproline-glycine, alanine-hydroxyproline-glycine, serine-hydroxyproline-glycine), or a mixture of amino acids (glycine, proline, hydroxyproline, and alanine at a ratio of 3:1:1:1) in fibroblast cultures. 104 This evidence can partially explain the variation in efficacy among different collagen peptides in improving skin functions.

It is important to note the remarkable heterogeneity across the clinical trials, including the dose and source of peptides, the characteristics of the participants, and the trial protocols, which potentially result in various outcomes. For instance, an oral dose of 2.5 g of bovine type I collagen increases skin hydration in women aged 35 to 55 years, 26 but not in those aged 45 to 60 years. 25 Stratum corneum hydration levels were increased following the oral intake of 1000 mg of peptides from the skin of sutchi catfish, 43 but not from that of Nile tilapia. 44 Similarly, peptides from the scales of Nemipterus virgatus, but not from those of tilapia, increased hydration. 46 , 48 , 54 The sources of peptides determine their influence on the cell functions and skin biophysical properties, possibly due to the differences in amino acid composition. 63 Moreover, formulation can affect the absorption of collagen and peptides in the intestine. Generally, substances in liquid form are absorbed more easily than tablets. Variations in formulation can affect clinical outcomes. This line of evidence suggests that, at the very least, the age of participants, the source, type of formulation, and the extraction techniques of peptides can influence clinical outcomes. However, the limited number of studies does not allow for any conclusions about which dose, source, and extraction techniques of peptides are effective for which cutaneous functions and in which populations.

In summary, oral administration of collagen peptides can improve multiple cutaneous biophysical properties, including stratum corneum hydration levels, TEWL, elasticity, and skin firmness through divergent mechanisms, such as stimulation of keratinocyte differentiation and fibroblast proliferation, hyaluronic acid and aquaporin 3 production, synthesis of collagen, expression of antioxidant enzymes, in addition to inhibition of inflammation and matrix metalloproteinases ( Figure 1 ). However, whether the variation in clinical outcomes across the studies is due to the sources and/or the composition of peptides is unclear. Moreover, the optimal dose of peptides remains to be explored although oral intake of hydroxyproline (Hyp)-containing peptides dose-dependently increases plasma levels of free Hyp and Hyp-containing peptides. 105 Variation in participant age, assessment sites, and methodologies makes cross-peptide efficacy comparisons difficult. The safety of these peptides, particularly with long-term use, warrants further evaluation.

Figure 1 The underlying mechanisms by which oral collagen peptides improve cutaneous biophysical properties. The arrows ↑ and ↓, indicate upregulation and downregulation, respectively.

Limitations

This review has some limitations. First, it only summarizes the evidence from studies published in English, which means that studies published in other languages are excluded. Second, studies from databases other than PubMed and Google Scholar were not included, even though these two databases account for most of the relevant publications. Moreover, due to the heterogeneity across the studies, no conclusion can be drawn about which sources or types of collagen/peptides have superior efficacy compared to others. Further studies are needed to assess the efficacy of various sources and types of collagen/peptides on different skin biophysical properties.